COVID-19 challenges and its therapeutics

Abstract

COVID-19, an infectious disease, has emerged as one of the leading causes of death worldwide, making it one of the severe public health issues in recent decades. nCoV, the novel SARS coronavirus that causes COVID-19, has brought together scientists in the quest for possible therapeutic and preventive measures. The development of new drugs to manage COVID-19 effectively is a challenging and time-consuming process, thus encouraging extensive investigation of drug repurposing and repositioning candidates. Several medications, including remdesivir, hydroxychloroquine, chloroquine, lopinavir, favipiravir, ribavirin, ritonavir, interferons, azithromycin, capivasertib and bevacizumab, are currently under clinical trials for COVID-19. In addition, several medicinal plants with considerable antiviral activities are potential therapeutic candidates for COVID-19. Statistical data show that the pandemic is yet to slow down, and authorities are placing their hopes on vaccines. Within a short period, four types of vaccines, namely, whole virus, viral vector, protein subunit, and nucleic acid (RNA/DNA), which can confer protection against COVID-19 in different ways, were already in a clinical trial. SARS-CoV-2 variants spread is associated with antibody escape from the virus Spike epitopes, which has grave concerns for viral re-infection and even compromises the effectiveness of the vaccines. Despite these efforts, COVID-19 treatment is still solely based on clinical management through supportive care. We aim to highlight the recent trends in COVID-19, relevant statistics, and clinical findings, as well as potential therapeutics, including in-line treatment methods, preventive measures, and vaccines to combat the prevalence of COVID-19.

Keywords: COVID-19; NCoV; Pneumonia; Prevention; Treatment; Vaccines.

Fig. 1

The nCoV Life Cycle: Stages and Targets The life cycle of nCoV in human cells may provide enlightenment for viral transmission and its potential therapeutic targets. Step-I: The nCoV is distinguished by spikes (S, club-like) on the surface and a distinctive replication scheme. Coronaviruses entry to the cell is based on the viral spike proteins binding to cellular receptors (such as angiotensin-converting enzyme 2 (ACE2)) and its priming by the action of host cell proteases. Step II & III: Once the viral RNA is untied inside the host cell, the translation of polyproteins is initiated. The nCoV genomic RNA encodes non-structural proteins (NSPs), which is crucial in synthesizing viral RNA, and the structural proteins essential for virion assembly. Step IV: To replicate structural protein, RNA replicase–transcriptase complex is required. With the help of endoplasmic reticulum bounds ribosomes, the structural proteins S1, S2, Membrane (M), Envelope (E) are translated and exhibited on its surface for the priming of virion assembly. The nucleocapsids (N) stay in the cytoplasm and are congregate from genomic RNA. Nucleocapsids join the virion precursor, transported to the cell surface from the endoplasmic reticulum through the Golgi Apparatus in small vesicles. Step V: By exocytosis, the mature virions are released from the infected cell's surface and set free to infect other host cells.

Fig. 2

Vaccines clinical trials status The graph represents the number of vaccines in various stages of the vaccine development process. The conventional pattern is observed having a bigger number of vaccines in preclinical trials than clinical trials (Phase-I to Phase-III) stages and the approved ones. To date, limited vaccines have granted emergency approval from WHO for use in the general population.